Copper is an essential element in biological systems by virtue of its coenzyme function in a number of enzyme systems. Two distinct inherited disorders of copper metabolism in humans have thus far been recognized: Menkes disease and Wilson's disease. Recent successful cloning of the genes for these two diseases suggests that in each case the abnormality is probably associated with defective intracellular trans-membrane copper transport. In particular case of Menkes disease, which is characterized by deficient enzyme copper content, it has been suggested that the specific transport defect may be associated with the microsomal membrane. For this reason, and in view of the lack of any information concerning intracellular copper transport, we have studied the uptake of cuprous copper in a model system composed of purified rat liver microsomal membranes. The use of monovalent copper in this instance is dictated by the probable state of this metal in the cytosol of the intact cell. Although time- and temperature-dependent copper uptake into microsomal vesicles has been observed, interpretation of the results has been hampered by a high background of non-specific, irreversible copper binding. It is conceivable that the use of stripped microsomes, i.e., microsomes free of attached ribosomal RNA, may serve to reduce this unwanted background.